tbuckley/cabot-search huggingface dataset:
Abstract 13561: Sex-Based Differences in Outcomes for Transcatheter Based Intervention: Insight From the National Inpatient Sample
Authors: IRIAGBONSE ASEMOTA, Muhammad Khawar Sana, Mahir Yilmaz, Hasan Hammo, Sean DeAngelo, Bharosa Sharma, Muhammad Usman Almani, Muhammad Usman, Emmanuel Akuna, Hafeez Shaka
Journal: Circulation (2022)

Introduction: Transcatheter aortic valve replacement (TAVR) is now firmly established as an alternative to surgical aortic valve replacement in the treatment of aortic stenosis in all risk groups. Sex differences may influence procedural outcomes. Our study aims to contribute further data on the impact of sex differences on patients who underwent TAVR using a nationally representative sample. Methods: Data were obtained from the combined National Inpatient Sample (NIS) 2016 and 2018. The NIS was searched for hospitalization for TAVR procedure using the ICD-10 PCS codes. Patients undergoing the TAVR procedure were then stratified by sex into male and female sex. Outcomes of interest include in-patient mortality, length of stay (LOS), Total hospital charge (THC), Post procedural complication, pacemaker implantation, cardiogenic shock, ischemic stroke, intra-aortic balloon pump insertion, post-procedural infection, and post-procedural kidney disease. Multivariate logistic and linear regression analysis was used accordingly to adjust for possible confounders. Results: There were over 105 million discharges in the combined 2016-2018 NIS database. The database contained hospitalizations for adult patients (aged ≥ 18 years) who were hospitalized for the TAVR procedure. Females had more TAVR procedures compared to men (54.1% vs 45.9%, P&lt;0.0001 and were older than men who underwent TAVR. There was similar in-patient mortality in both group (1.7% vs 1.2%, AOR: 1.21, P=0.072, 95% CI 0.98- 1.51). Women had lower rate of cardiogenic shock (AOR: 0.78, P=0.009, 95% CI 0.65-0.94), pacemaker implantation (AOR: 0.84, P=0.001, 95% CI 0.76-0.93) compared to men. Women had higher odds of post-procedural complications compared to men (AOR: 1.18, P=0.001, 95% CI: 1.07-1.29. There were similar rates of ischemic stroke (AOR: 1.23, P=0.502, 95% CI 0.66-2.31), postprocedural kidney injury (AOR: 1.65, P=0.278, 95% CI 0.66-4.12) in women compared to men. In addition, there was no difference in total charge and length of hospital stay. Conclusions: Women had increased post-procedural complications compared to men in regard to TAVR, however, mortality is similar in both groups. There was no difference in resource utilization and length of stay between both sexes.
Abstract 13464: Association of Left Atrial Hemodynamics by Magnetic Resonance Imaging With Long Term Outcomes in Patients With Cardiac Amyloidosis
Authors: Punit Arora, Mina M Benjamin, Muhammad Munir, Amir Darki, MAX LIEBO, Mingxi Yu, Mushabbar Syed, Menhel Kinno
Journal: Circulation (2022)

Introduction: We investigated left atrial (LA) function and strain by MRI in patients with cardiac amyloidosis (CA) and their associations with clinical outcomes. Methods: We conducted a retrospective case control study of 51 CA patients (24 transthyretin [ATTR] and 27 systemic [AL]) and 51 age, gender, and race matched controls without cardiovascular disease who underwent MRI in sinus rhythm. We measured LA function and strain parameters including indexed volumes (LAVi), ejection fraction, expansion index, reservoir (εR), contractile (εCT), and conduit (εCD) strain. A multivariate regression model was adjusted for age, hypertension, NYHA class, modified staging system (using Troponin-I, BNP, and GFR) and left ventricular ejection fraction (LVEF). We used endpoints of all-cause mortality and a composite endpoint of heart failure hospitalization (HFH) or death. Results: Mean age was 65.3 for AL vs 76.2 for ATTR. ATTR patients had higher LAV, indexed LV and RV end systolic volumes and lower LVEF than AL patients. CA patients had significantly lower LA strain (11.5, 4.7, 6.8 vs 38.2, 14.2, 24 for εR, εCT, εCD respectively) and higher LAVs than controls. Median follow up was 12.6 months. εCT (OR 0.6, CI: 0.41-0.89), minimum LAVi (OR 1.06, CI: 1.02-1.13) and maximum LAVi (OR 1.08, CI: 1.01-1.15) were associated with the composite outcome of death or HFH. Cox Hazard regression models showed a difference in the composite outcome as LAVi increases and ↋CT is reduced. χ2 statistic were 23.1 for ↋CT versus 18.4 for LAVi (P=0.04, 0.01). Conclusion: In our retrospective study of CA patients, εCT, minimum and maximum LAVi were significantly associated with the composite outcome of death or HFH.
Abstract 13465: Digital Health and Multifaceted Interventions to Help Manage Cardiovascular Patients in a Resource-Constrained Area in Brazil Before and During COVID-19 Pandemic
Authors: Milena S Marcolino, Christiane C Cimini, Junia X Maia, Vania Almeida Pinto, Victor S Schulthais Chagas, James Batchelor, Antonio Luiz P Ribeiro
Journal: Circulation (2022)

Introduction: During the COVID-19 pandemic, social isolation led to a reduction in the number of consultations of patients with hypertension and diabetes mellitus (DM) , which may cause serious complications. Objective: To assess the effect of the pandemic on the control of hypertension and DM in primary care. Additionally, to develop and assess usability of a digital solution to improve patient monitoring. Methods: Quasi-experimental study. Patients ≽30 years-old with diagnosis of hypertension or DM from 34 primary health care centers from 10 Brazilian municipalities were assessed from Jun/2017 to Dec/2020. Data on the number of consultations, systolic, diastolic blood pressure (SBP, DBP) and glycohemoglobin levels were collected. A decision support system (DSS) was developed, to be used by community health workers (CHW), to identify patients with uncontrolled diseases during household visits. Software usability was assessed by a panel of experts. Results: From 5,070 patients (mean age 56.0 [IQR 48.0-62.0], 66.4% women), 94.9% had hypertension and 27.0% DM. There was a significant reduction in the weekly number of consultations before vs. after social restriction, (107 [IQR 60, 153] vs (20 [IQR 7, 29]), p&lt;0.001). Only 772 patients (15.2%) returned for consultation since the beginning of the pandemic. They had lower SBP (120.0, IQR 120.0-140.0 mmHg) and DBP (80.0, IQR 80.0-80.0 mmHg), comparing to individuals who did not return (SBP: 130.0, IQR 120.0-140.0 mmHg; DBP: 80.0, IQR 80.0-90.0 mmHg; p&lt;0.001). There was no difference in glycohemoglobin levels. The expert panel agreed the DSS may identify patients at risk, and can be incorporated into the CHW routine. Up to March 2021, over 17,000 registries were performed using the app. Conclusion: COVID-19 pandemic caused a significant reduction in the number of consultations of patients with hypertension and DM in PHC. The DSS was considered useful, and it was well accepted by the CHW.
Abstract 13309: Specific Deletion of Microrna1’S Biophysical Action Causes a Functional Deterioration of the Heart and Increases the Vulnerability to Arrhythmias
Authors: Feng Tang, Xiaoping Wan, Dandan Yang, Ege Kacira, Xianyao xu, Neill Schwieterman, Daniela Ponce, Loren E Wold, Thomas Hund, Peter J Mohler, Isabelle Deschenes, Jidong A Fu
Journal: Circulation (2022)

MicroRNAs (miRs) are involved in most biological events via a broadly-recognized RNA interference (RNAi) mechanism. miR1, encoded by miR1-1 and miR1-2 genes, is the predominant miRs of the heart and plays a critical role in heart development and cardiac diseases. Previous studies of miRs have focused on the canonical RNAi mechanism. Recently, we discovered a novel biophysical action of miR and found that miR1 physically binds to Kir2.1 and directly suppresses the inward rectifier potassium current (I K1 ). However, the physiological significance of this newly-discovered biophysical action of miR remains unknown. Importantly, we found that a human single nucleotide polymorphism (hSNP)-hSNP14A/G (rs776480338), in which the 14th nucleotide of miR1 is mutated from A to G, specifically disrupts this biophysical action while maintaining its RNAi function. We then created a single nucleotide mutation of hSNP14A/G on mouse miR1-1 and miR1-2 genes by CRISPR/Cas9 technology and have successfully developed 14G-mutated homozygous transgenic mice (14G-Homo), in which the biophysical function of miR1 is specifically removed while the RNAi function is maintained. We found that 14G-Homo mice had higher mortality than wild-type (WT) mice. Echocardiogram showed that, compared to WT hearts, adult 14G-homo heart (2-month age) had significantly lower ejection fraction and fractional shortening with a thinner wall of the left ventricle, which became more severe at the age of 6 months; some mice developed severe heart failure. Surface ECG showed that 14G-Homo hearts had a slower heart rate and the prolonged QRS interval and QT interval. Optical mapping revealed a slower conduction velocity in the 14G-Homo heart with high inducibility of ventricular arrhythmias. Patch clamping of isolated ventricular cardiomyocytes showed that, compared to WT cells, 14G-homo cardiomyocytes had an increased amplitude and prolonged duration of action potential with bigger I K1 and L-type calcium currents. In conclusion, our discoveries demonstrate that the biophysical action of miR1 is deeply involved in maintaining the homeostasis of the heart. Specific deletion of the biophysical function causes a functional deterioration of the heart and increases the vulnerability to arrhythmias.
Abstract 13631: Cardiovascular Risk Profile Among Reproductive Aged Women in the United States: The Behavioral Risk Factor Surveillance System (2015-2020)
Authors: Ellen Boakye, Yaa A Kwapong, Sadiya S Khan, Mamas Mamas, Amanda Perak, Pamela S Douglas, Pradeep Natarajan, Roger Blumenthal, Khurram Nasir, Allison Hays, Michael J Blaha, Garima Sharma
Journal: Circulation (2022)

Introduction: Suboptimal cardiovascular health (CVH) is associated with adverse pregnancy outcomes and long-term CV risk. Studies examining contemporary trends in CV risk factors (RF) and suboptimal CVH among US women of reproductive age are limited. Methods: We used the 2015 - 2020 Behavioral Risk Factor Surveillance System, a nationally representative survey of US adults, to conduct this serial cross-sectional study. We restricted our sample to nonpregnant reproductive-aged women (18-44 years) without CVD (n=336,102). We calculated the prevalence of each CV RF (current smoking, hypertension, diabetes, hypercholesterolemia, physical inactivity, poor diet, and overweight/obesity) and suboptimal CVH (≥2 RF) for each year and examined trends between 2015 and 2020 Results: Between 2015 and 2020, diabetes prevalence remained relatively stable (2.9% to 3.0%; p=0.09) while overweight/obesity prevalence increased (53.1% to 58.4%; p&lt;0.001). Conversely, prevalence of current smoking declined (16.0% to 12.4%; p&lt;0.001). Also, between 2015 and 2019, hypertension prevalence remained stable (9.9% to 10.1%; p=0.57) while there was an increase in the prevalence of physical inactivity (49.1% to 51.6%; p&lt;0.001) and poor diet (80.2% to 81.6%; p=0.003) but a decline in prevalence of hypercholesterolemia (16.2% to 12.6%; p&lt;0.001). The prevalence of suboptimal CVH increased modestly from 72.4% (71.6%-73.3%) in 2015 to 75.9% (75%-76.7%) in 2019 (p&lt;0.001). Significant increases in the prevalence of suboptimal CVH were observed among non-Hispanic White (69.8% to 72.6%) and Hispanic (75.1% to 80.3%) but not among non-Hispanic Black (82.7% to 83.7%) and Asian women (68.1% to 73.2%). State-level prevalence of suboptimal CVH in 2019 varied significantly Conclusions: There has been a modest increase in suboptimal CVH among US women of reproductive age. Thus, preventive efforts are needed to improve CVH in women, particularly among subgroups at increased risk of suboptimal CVH.
Abstract 13600: Performance of a Multi-Metabolite Score Added to a Risk Prediction Model for Incident Diabetes in Young Adults: The CARDIA Study
Authors: Konrad T Sawicki, Hongyan Ning, Keenan Fine, Norrina B Allen, Mercedes R Carnethon, James D Otvos, Ravi V Shah, Venkatesh L Murthy, John T Wilkins
Journal: Circulation (2022)

Introduction: The Finnish Diabetes Risk Score (FINDRISC) is a risk prediction tool used to estimate absolute risk for type 2 diabetes mellitus (DM), a critical risk factor for cardiovascular disease. The Diabetes Risk Index (DRI) is a multi-metabolite DM risk score developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from six lipoproteins, and the branched chain amino acids, valine and leucine. Although the DRI is independently associated with future DM in middle-aged adults, the performance of this novel biomarker when added to FINDRISC to predict incident DM in young adults is not known. Hypothesis: The addition of DRI to FINDRISC will improve the 10-year(y) risk prediction of DM across all ages in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods: We measured the DRI using NMR spectroscopy in CARDIA participants across different age categories: 20-30y (n=1,911), 30-40y (n=2,716), 40-50y (n=2,232). We used Cox proportional hazards regression to evaluate the association of the DRI with incident 10-y DM risk. We assessed FINDRISC model performance using C-statistic and continuous Net Reclassification Index (NRI) with and without the addition of the DRI as a covariate. Results: DRI was associated with 10-y DM risk across all age categories. Addition of the DRI modestly improved the C-statistic in the 30-40-y age category. Addition of DRI to FINDRISC improved the overall NRI in the 30-40- and 40-50-y age categories. The non-event NRI was significant across all 3 age categories and reclassified 25-36% of participants who did not develop DM to a lower estimate of incident DM risk (Table). Conclusions: Among young and middle-aged adults, DRI scores were associated with 10-y risk of DM. The addition of DRI to FINDRISC led to improvements in reclassification of DM risk, as the addition of DRI to FINDRISC correctly classified up to 36% of participants who did not develop DM (over 10y) to a lower estimate of incident DM risk.
Abstract 14364: Protein Kinase C Beta II Inhibitor Provides Cardiovascular Protection When Combined With Conjugated Myristic Acid and Trans-Activator of Transcription in Porcine Ischemia-Reperfusion Injury
Authors: Kayla P Harrell, Arjun Nair, Desmond Boakye Tanoh, Sunit Singh, Emily Andrews, Tameka Dean, Qian CHEN, Robert Barsotti, Lindon Young
Journal: Circulation (2022)

Prompt reperfusion is vital to resuscitating ischemic myocardium. However, cardiomyocyte death still occurs due to ischemia-reperfusion (I/R) injury, which is mediated in part by oxidative stress. Major sources of reactive oxygen species (ROS) during I/R are NADPH oxidase (NOX-2) and mitochondria, which are principally activated by protein kinase C βII (PKCβII). Previously, myristic acid (Myr) and trans-activator of transcription (Tat) conjugated PKCβII inhibitor (Myr-Tat-PKCβII-; N-Myr-Tat-CC-SLNPEWNET) exhibited cardioprotective effects in ex vivo rat hearts. In this study, we hypothesize that Myr-Tat-PKCβII- will mitigate cardiac injury in an in vivo porcine myocardial I/R model compared to scrambled peptide controls. Male Yorkshire pigs (38-50kg) underwent regional I(1hr)/R(3hrs) through balloon-assisted occlusion of the second diagonal branch of the left anterior descending coronary artery (LAD) supplying ~40% of the anterior portion of the myocardium. During reperfusion (balloon deflation), a bolus of Myr-Tat-PKCβII- or scrambled control was infused into the LAD. Cardiac function was evaluated as the relative change in ejection fraction (EF) at the end of 3hr reperfusion compared to baseline. Serial measurements of serum creatine phosphokinase (CPK), troponin I, and myoglobin were evaluated to assess cardiac injury. Post-reperfused hearts were stained with Evans Blue dye to identify the area at risk (AR) and 1% triphenyltetrazolium chloride to demarcate the area of necrosis (AN). Infarct size (AN/AR), EF, and cardiac injury markers were analyzed via Student’s t-test. Myr-Tat-PKCβII- preserved EF with a relative change of 1.2±2.8% compared to 8.9±2.2% in control hearts (p&lt;0.05) from mean baseline EF (61.4±0.5%). Myr-Tat-PKCβII- significantly decreased myoglobin levels at 1hr reperfusion (135±132ng/mL, n=4) compared to scrambled control (1022±346ng/mL, n=3 p&lt;0.05). Myr-Tat-PKCβII- reduced infarct size to 13.5±3.9% (n=4) compared to scrambled control hearts (27.5±7.9%, n=6). CPK and troponin I levels were comparable in both groups. These results suggest Myr-Tat-PKCβII- mitigates cardiac injury when given at reperfusion onset. Future studies will examine Myr-Tat-PKCβII- in an 8 week in-vivo, porcine MI survival study.
Abstract 14065: Functional and Structural Alterations in Stress-Related Neural Networks Implicated in Atherosclerosis
Authors: Charbel Gharios, Sarah Boukezzi, Lisa Shin, James Murrough, Helena Chang, Ming Yin Y Lun, Mandy van Leent, Michael Osborne, Ahmed A Tawakol, Zahi A Fayad
Journal: Circulation (2022)

Introduction: While a link between chronic stress and cardiovascular disease (CVD) is well established, the neurocircuit alterations underlying this association remain unclear. We leveraged advanced multimodal imaging to gain insights into neurocircuit alterations that associate with atherosclerosis. Methods: Individuals with posttraumatic stress disorder (PTSD), trauma-exposed controls without PTSD (TC), and healthy controls (HC) were prospectively enrolled. Participants underwent whole-body 18 F-fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG-PET/MR) imaging. Stress-related neural network activity (SNNA) was assessed on PET as amygdala metabolic activity relative to regulatory (ventromedial prefrontal cortex [vmPFC]) activity. The structural integrity of the uncinate fasciculus, the major white matter tract connecting the amygdala to vmPFC, was assessed using diffusion tensor imaging (DTI). Atherosclerotic burden was assessed on MR as vessel normalized wall index and standard deviation (SD) of vessel wall thickness. Results: Of 91 participants (24 PTSD, 42 TC, 24 HC), 57% were female, and the median age was 37 years. Compared to controls, individuals with PTSD had higher SNNA (Fig 1A) and lower uncinate fasciculus integrity (Fig 1B). SNNA and uncinate fasciculus integrity were negatively correlated (r = - 0.30, p=0.008). Those with PTSD had higher ascending aorta normalized wall indices (p=0.018, adjusted for Framingham risk score). Notably, the SD of carotid wall thickness correlated positively with SNNA and negatively with uncinate fasciculus integrity (Fig 1C &amp; D). Conclusion: These findings suggest that increases in the amygdala relative to vmPFC metabolic activity or disruptions of their structural interconnections may potentiate atherosclerosis. Interventions targeting this stress-related neural network may reduce adverse brain-heart interactions and related cardiovascular disease burden.
Abstract 13470: Circulating microRNA-122-5p is Associated With a Lack of Improvement in Left-Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes via Extracellular Vesicles
Authors: M. Rabiul Hosen, Reinier Boon, Joseph Moore, Shizuka Uchida, Eicke Latz, Felix Jansen, Georg Nickenig
Journal: Circulation (2022)

Transcatheter aortic valve replacement is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic AVS. However, a specific role for circulating microRNAs in the improvement of cardiac function for patients after TAVR has not yet been investigated. Methods: Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs were significantly deregulated in AVS patients on day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=-0.264 and p=0.015) and at six months (r=-0.328 and p=0.0018). Results: By utilization of patient-derived samples and a murine AVS model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced AVS mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in ECs in comparison to cardiomyocytes. Co-culture, copy-number analysis, and immunofluorescence demonstrated that miR-122-5p can be shuttled via large EVs from ECs into cardiomyocytes. Gain- and loss-of-function suggested that EV-shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miR-pull down, EMSA, and RNA-IP experiments confirmed that miR-122-5p interacts with the RBP, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling, miR-122-5p reduces the expression of the anti-apoptotic gene BCL2 , by binding to its 3' untranslated region to inhibit its translation. Conclusion: Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR.
Abstract 13713: Myocarditis and Coronary Vasospasm in a Patient With Antiphospholipid Syndrome and MINOCA
Authors: Goutham Ravipati, Mason Marcus, Jeomi Okwara
Journal: Circulation (2022)

Background : The prevalence of MINOCA in patients with antiphospholipid syndrome (APLS) is estimated to be 20%. Frequent causes in this population include coronary vasospasm, microcirculatory dysfunction and takotsubo cardiomyopathy. Objective : This case reveals myocarditis and coronary vasospasm as newly described complications of APLS associated MINOCA and illustrates the use of CMR to differentiate ischemic injury from myocarditis in this population. Case : A 40-year-old female presented with two-days of left-sided, substernal, pleuritic, and radiating chest pain associated with dyspnea. Admission ECG showed 0.5mm ST elevations in the inferior leads with ST depression in aVL. She had an initial high sensitivity troponin of 1531 ng/L, NT-proBNP of 18,357 pg/mL, baseline creatinine of 1.53 mg/dL, platelets of 95,000/μL, hemoglobin of 8.4 g/dL, and a subtherapeutic INR of 1.1 on warfarin. An emergent catheterization showed no coronary artery disease or evidence of SCAD. TTE showed hypokinesis of inferior and lateral walls with an LVEF of 45% and CTA chest ruled out pulmonary embolism. The patient’s admission was complicated by rising troponins to a peak of 9790 ng/L, oliguric renal failure requiring continuous renal replacement therapy, and fever. Patient was medically managed for presumed myocardial infarction and repeat TTE two days after catheterization showed a recovered LVEF of 59%. CMR showed a transmural infarct of the basal and inferior walls with signs of microvascular obstruction and diffuse patchy late gadolinium enhancement of the LV midwall, consistent with myocarditis. An infectious workup for myocarditis was negative. Patient was discharged home on warfarin, aspirin, and amlodipine. Conclusion : MINOCA is more common in patients with APLS, although coronary vasospasm and myocarditis have not been described in the same patient. CMR is useful to differentiate the etiology of ischemic injury following successful diagnosis of MINOCA.